Research on the Stability of a Rabbit Dry Eye Model Induced by Topical Application of the Preservative Benzalkonium Chloride

Dry eye is a common disease worldwide, and animal models are critical for the study of it. At present, there is no research about the stability of the extant animal models, which may have negative implications for previous dry eye studies. In this study, we observed the stability of a rabbit dry eye model induced by the topical benzalkonium chloride (BAC) and determined the valid time of this model.). Decreased levels of mucin-5 subtype AC (MUC5AC), along with histopathological and ultrastructural disorders of the cornea and conjunctiva could be observed in Group BAC-W4 and particularly in Group BAC-W5 until day 21.A stable rabbit dry eye model was induced by topical 0.1% BAC for 5 weeks, and after BAC removal, the signs of dry eye were sustained for 2 weeks (for the mixed type of dry eye) or for at least 3 weeks (for mucin-deficient dry eye)

The scores for sodium fluorescein staining in all groups.

<p>Compared with the pre-treatment group, there were significant differences on days 0, 7 and 14 after the cessation of BAC treatment in the BAC-W2, BAC-W3, BAC-W4, and BAC-W5 groups.</p

Representative images from transmission electron microscopy showing the conjunctival epithelial ultrastructure.

<p>Compared with normal eyes, fewer goblet cells and secretary granules were observed on day 0 in Groups BAC-W2 and BAC-W3, and on days 0, 7, and 21 in Group BAC-W4. This loss of goblet cells and secretary granules was particularly pronounced in Group BAC-W5 on all of the days that were studied. Chromatin condensation and peripheral migration could be observed on days 0, 7, and 21 in Group BAC-W5.</p

Representative examples of CIC in each group.

<p>Each group showed evidence of having an abundance of goblet cells, and the goblet cells were oval in shape and full when normal. On day 0, there were only a few goblet cells in all of the groups, and these goblet cells were irregularly shaped. This difference from baseline could be observed on days 0, 7 and 14 in Group BAC-W2 and on days 0, 7, 14, and 21 in groups BAC-W3, BAC-W4 and BAC-W5.</p

Representative images from scanning electron microscopy.

<p>Compared with normal eyes, there were fewer microvilli, and these microvilli were shorter and less regularly arranged on days 0 and 7 in Groups BAC-W2, BAC-W3 and BAC-W4, and on days 0, 7, and 21 in Group BAC-W5.</p

Representative images from transmission electron microscopy that revealed the ultrastructure of the corneal epithelium.

<p>Compared with normal eyes, vacuoles between the cells could be observed on day 0 in Group BAC-W2 and on days 0, 7, and 21 in Groups BAC-W3, BAC-W4. These vacuoles were particularly prominent among samples from Group BAC-W5.</p

The results of Schirmer's tests in all groups.

<p>Schirmer's test results show decreased aqueous tear secretion compared to pre-treatment secretion levels on days 0, 7 and 21 after the cessation of BAC treatment. *P<0.05, **P<0.01, ***P<0.001, respectively. Compared with pre-treatment, the differences were statistically significant on days 0 and 7 in the BAC-W2, BAC-W3, and BAC-W4 groups as well as on days 0, 7 and 14 in Group BAC-W5. The values shown are average wetted lengths ± standard deviations.</p